N,N-Diethylaniline → 2-chloro-3-ethoxypyridine

HRID 1990836Notes

Reaction equation

HRID 1990836 reaction equation
[CH2:1]([O:3][C:4]1[C:5](O)=[N:6][CH:7]=[CH:8][CH:9]=1)[CH3:2].C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)([Cl:24])=O>O>[Cl:24][C:5]1[C:4]([O:3][CH2:1][CH3:2])=[CH:9][CH:8]=[CH:7][N:6]=1

Participants

5

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178466714HCID 178466714, compound

Product 1

HCID 122934752-chloro-3-ethoxypyridineYield 71%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3-ethoxy-pyridin-2-ol (4.0 g, 28.8 mmol, 1.0 equiv), N,N-diethylaniline (4.61 mL, 4.29 g, 28.8 mmol, 1.0 equiv) and phosphorus oxychloride (2.62 mL, 4.41 g, 28.8 mmol, 1.0 equiv) was heated to 150° C. under microwave irradiation for 20 min. The crude reaction mixture was poured into water (100 mL), the solution adjusted to pH 7 and extracted with dichloromethane (3×100 mL). The combined organic phases were dried over MgSO4, the solvent removed by evaporation under reduced pressure and the crude material purified with column chromatography on silica eluting with hexane/ethyl acetate (4:1) providing 3.2 g (71%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.50 (t, J=7.0 Hz, 3H), 4.12 (q, J=7.0 Hz, 2H), 7.18 (d, J=3.2 Hz, 2H), 7.98 (t, J=3.2 Hz, 1H). MS (ISP): 157.7 [M+H]+.

Workup

  1. customThe crude reaction mixture
  2. extractionextracted with dichloromethane (3×100 mL)
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. customthe solvent removed by evaporation under reduced pressure
  5. customthe crude material purified with column chromatography on silica eluting with hexane/ethyl acetate (4:1)

Sources & evidence

ORD record
ord-2946bd3eaef945f7b7678199de872183
Source dataset
uspto-grants-2010_01
Patent number
US07645753B2

Reaction notes

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